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CONFIDENTIAL & PROPRIETARY Corporate Presentation January 2025 BioCryst Pharmaceuticals, Inc.
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Forward-looking statements 2 BioCryst’s presentation contains forward-looking statements, including statements regarding future results, preliminary, unaudited revenue results, and forward-looking financial information and company performance, achievements, or future market share or size. These statements are subject to known and unknown risks, uncertainties and other factors which may cause actual results, performance, achievements, or market share or size to be materially different from any preliminary, unaudited revenue results and future results, performance, achievements, or market share or size expressed or implied in this presentation. These statements reflect our current views with respect to future events and are based on assumptions and are subject to risks and uncertainties. You should not place undue reliance on the forward-looking statements. For additional information, including important risk factors, please refer to BioCryst’s documents filed with the SEC and located at ir.biocryst.com/financial-information/sec-filings.
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BioCryst: durable, profitable growth through the decade with pipeline optionality 33 Financially Independent with near-term path to profitability with near-term milestones growing to $1B peak annual sales Clinical Pipeline Marketed Product
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2024 highlights and 2025 outlook 4 • 2024 Results: $437M global ORLADEYO® revenue (34% growth) and $450M total revenue • Over 1,200 US prescribers • Commercially available in over 30 countries • ORLADEYO pediatric program on track for regulatory submission in 2025 • BCX17725 (Netherton syndrome) and avoralstat (DME) advancing into patients in 2025 • Achieved goal for full-year 2024 operating profit1 • On track for sustainable quarterly positive EPS and cash flow in 2H25 • Revenue expected to grow at ~20% CAGR over next 3 years, vs. ~5% for operating expenses COMMERCIAL EXCELLENCE CLINICAL PROGRESS BUILDING SUSTAINABLE PROFITABILITY 2025 REVENUE GUIDANCE • ORLADEYO: $515-535M • Total revenue: $540-560M 1. Excluding stock-based compensation expense
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Strong ORLADEYO growth to continue in 2025 5 ORLADEYO REVENUE QUARTERLY & QUARTERLY AVERAGE BY YEAR ($M) Revenue ($M) 123 252 326 437 515-535 Growth ($M) +123 +129 +74 +111 +78-98 Growth (%) – +105% +30% +34% +18-22% 0 20 40 60 80 100 120 140 160 1Q 2Q 3Q 4Q 1Q 2Q 3Q 4Q 1Q 2Q 3Q 4Q 1Q 2Q 3Q 4Q 1Q 2Q 3Q 4Q 2021 2022 2023 2024 2025*2025 Guidance 1Q 2Q 3Q 4Q
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6 ASSUMPTIONS • 15-20% gross-to-net on Paid shipments • Compliance in low-90s% $310 $295 $100 $95 $800 2023 Exit Rate Patient Growth Reimbursement Price 2029 Revenue 1,104 Paid + PAP1 patients with 71.5% Paid ~200 annual net patients added, 2024-2029 Improve rate of Paid to 85% Modest average price increases 2024-2029 1. PAP is the company’s long-term patient assistance program Path to $800M US revenue in 2029
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REAL WORLD EVIDENCE: patients with HAE Type 1 and 2 have significant and sustained attack reduction on ORLADEYO 7 • Median attack rate of 1/3rd of an attack per month in a study population of over 450 patients MONTHLY HAE ATTACK RATES BEFORE AND AFTER BEROTRALSTAT INITIATION Source: Sustained Real-World Attack Reductions Following Berotralstat Initiation Among Patients with Hereditary Angioedema with C1-Inhibitor Deficiency Presented at the ACAAI Scientific Meting 2024 • October 24-28, 2024 • The primary reason for reduced patient counts over time was that patients had not been on ORLADEYO long enough to be evaluated at all time points • Only 68 (14.6%) out of 466 patients in this study discontinued therapy
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REAL WORLD EVIDENCE: patients with HAE-nl-C1-inh have significant and sustained attack reduction on ORLADEYO 8 • Median attack rate of <1 per month in study population of over 350 patients • Excellent attack reduction and control for a population that has struggled to find effective therapy MONTHLY HAE ATTACK RATES BEFORE AND AFTER BEROTRALSTAT INITIATION Source: Sustained Real-World Attack Reductions Following Berotralstat Initiation Among Patients with Hereditary Angioedema without C1-Inhibitor Deficiency Presented at the ACAAI Scientific Meting 2024 • October 24-28, 2024 • The primary reason for reduced patient counts over time was that patients had not been on ORLADEYO long enough to be evaluated at all time points • Only 75 (21.2%) out of 353 patients in this study discontinued therapy
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Single Interaction & Decision Single Simulation Run Prophy Acute Only No HAE Med New Patient Full Market Simulation Approach 1. A patient, physician, and payer are randomly selected from survey respondents. 2. The model evaluates individual prescribing decisions based on patient preference, physician preference & payer approval within a framework of market dynamics (e.g., awareness, adoption, launch timing) 3. For a single simulation run, the process is repeated 30 times for each patient category 4. The simulation is then repeated 50 times (6,000 interactions) to create a generalized distribution, then scaled and weighted to HAE total population Comprehensive annual research + market simulation 9 OUR MODEL STARTS WITH PREFERENCE AND SIMULATES 6,000 MARKET INTERACTIONS BETWEEN HCPS, PATIENTS, & PAYERS Research Sample* Market Model Simulation (Monte Carlo) PATIENTS PHYSICIANS PAYERS n=100 HAE patients n=100 AIs**, and n=75 non-AIs** n=56 decision makers covering over 200 million total lives. Modeling Process - Visual Example 1 4 3 2 1 2 3 4 * Choice-based conjoint ** HAE treaters: Allergists & Immunologists
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Monte Carlo simulation outcome: U.S. prophy market share 10 ORLADEYO REACHES A STEADY STATE OF OVER 2,000 PATIENTS IN U.S. DURING 2028, EVEN AS NEW PRODUCTS GAIN SHARE 20% 21% 22% 24% 25% 24% 24% 24% 23% 23% 0% 20% 40% 60% 80% 100% 2024 2025 2026 2027 2028 2029 2030 2031 2032 2033 Prophylaxis Patient Share Orladeyo Takhzyro Haegarda Other Prophy Garadacimab Donidalorsen Deucrictibant Navenibart Estimated Prophylaxis Patients* Source: BioCryst Internal Market Research Study (Conducted Jun 2024) **Other Prophy: Any other current medication (including acute) taken prophylactically for HAE 7,200 8,100 8,800 9,300 ** *Source: 2018-2023 administrative claims data
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11 *ORLADEYO (age ≥ 2 years), BCX17725, and avoralstat are investigational and have not been deemed safe and effective by the FDA. †Proof of Concept is typically Phase 1 or 2. ‡Pivotal is typically Phase 3. ASSET PROGRAM LEAD OPTIMIZATION PRE - CLINICAL PROOF OF CONCEPT † PIVOTAL ‡ APPROVED / COMMERCIAL ORLADEYO® (berotralstat) Oral Plasma Kallikrein Inhibitor Hereditary Angioedema (HAE) ORLADEYO ® (berotralstat) Oral Plasma Kallikrein Inhibitor (age ≥2 years) Hereditary Angioedema (HAE) BCX17725 Protein Therapeutic Netherton Syndrome Avoralstat Ocular Plasma Kallikrein Inhibitor Diabetic Macular Edema (DME) Oral C5 Inhibitor Complement-Mediated Diseases Oral C2 Inhibitor Complement-Mediated Diseases Bifunctional Complement Inhibitor Complement-Mediated Diseases Our pipeline
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This is BIG: bringing ORLADEYO to children 12 • Despite significant innovation in HAE prophylaxis for adults, there is still high unmet need in children • Injectable therapies are the only FDA-approved options for children ages 2 to <12 • Positions ORLADEYO to be the market leading prophylaxis for children (~500 patients in US) New dosage form: granules (2x3 mm) APeX-P • Ages 2 to <12 • Open label, multi-center • Safety & PK study • Analysis completed - submission planning underway On track for NDA filing in 2025
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Treating Netherton syndrome (NS) with a targeted KLK5 inhibitor: BCX17725 1. Based on healthcare claims analysis Image: https://www.nethertonsyndrome.com/about-nethertons.php High unmet need Severe, rare, genetic and lifelong disease with no approved targeted therapies Validated target Well-understood biological cause: mutation in SPINK5 gene BCX17725 functionally replaces the missing protein Under- diagnosed Population Diagnosed US population of ~1,6001 with potential to grow to 3,000- 5,000 with greater diagnosis and treatment Next milestone: initial data in 2025
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BCX17725 addresses the underlying disease biology in Netherton syndrome 141. Petrova E and Hovnanian A. Exp Opin Orphan Drugs (2022) 8(11): 455-487 • Patients with NS have a mutation in the SPINK5 gene which causes a deficiency in the SPINK5 protein • The SPINK5 protein is an important natural regulator of KLK5, a serine protease involved in skin turnover • Unregulated KLK5 activity causes symptoms of NS by preventing formation of healthy skin barrier • BCX17725 targets KLK5, providing functional replacement of the missing regulator protein to correct disease biology • BCX17725 has the potential to improve both dermatologic and atopic disease symptoms HEALTHY SKIN NS SKIN SPINK5 KLK KLKKLK KLK Uppermost epidermal layers neutrophils allergen bacteria Modified from Petrova and Hovnanian, 2020 Expert Opinion Orphan Drugs1
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Addressing DME with a potent plasma kallikrein inhibitor: avoralstat suprachoroidal injection1 15 Right drug + delivery Alternative MOA Compelling evidence for plasma kallikrein activity in DME pathobiology New options are needed: up to 40% of patients have persistent DME despite anti-VEGF treatment Avoralstat has ideal properties for ophthalmic dosing: high potency and low solubility/depot effect Potential for disease modifying outcomes + extended dosing interval ~1.5M DME patients in US Est. $4B VEGF market by 2028 1. SCS Microinjector® is licensed from Clearside Biomedical, Inc.; SCS, suprachoroidal space Next milestone: begin patient studies in 2025 Significant market opportunity
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Avoralstat: a potent drug targeting DME 16 • Hyperglycemia damages retinal vasculature • Damaged endothelium activates plasma Kallikrein (pKal) • Elevated pKal levels seen in vitreous of DME patients • Elevated pKal produces bradykinin leading to vascular leakage • Avoralstat blocks pKal and bradykinin production • Avoralstat has similar effect to VEGF inhibitors in well-established non- clinical model Potential to treat all DME Patients via VEGF-independent pathway BK, bradykinin; HK, high molecular weight kininogen 1. Trinh HM, et al. World J Pharmacol. 2016;5(1):1-14. 2. Yang S, et al. Front. Pharmacol. 2021;12:727870. 3. Kita T, et al. Diabetes. 2015;64(10):3588-3599. 4. Lang GE, et al. TSVT. 2020;9(4)1-12.
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Suprachoroidal depot leads to 3+ months of sustained avoralstat levels in the retina1 1. BioCryst Pharmaceuticals nonclinical data on file 2025
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18 Avoralstat has similar effect to VEGF inhibitors in well- established nonclinical model1 Avoralstat (7 Days post dose)Pre-Dosing Vascular leakage Vascular Stability Vascular leakage Avoralstat (6 Days post dose) Vascular stability 1. BioCryst Pharmaceuticals nonclinical data on file 2025., Kumar et al. Int J Ophthalmol. 2022 Jan 18;15(1):15-22. Pre-Dosing
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Financial independence and clear path to profitability 19 Full year positive EPS & cash-flow 2024 2025 2026 1. Excluding stock-based compensation expense Full year operating profit1 Approach quarterly positive EPS & cash- flow in 2H
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Key milestones in 2025 20 File pediatric NDA for ORLADEYO Begin avoralstat clinical evaluation in patients Obtain initial BCX17725 clinical data Approach sustainable quarterly positive EPS & cash flow 2025 2025 2H25 2H25
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Finance summary 21 (Figures in millions) Q3 2024 CASH POSITION Cash, cash equivalents, restricted cash & investments at December 31, 2023 $391 Cash, cash equivalents, restricted cash & investments at June 30, 2024 $338 Cash, cash equivalents, restricted cash & investments at September 30, 2024 $352 Senior credit facilityA $324 2025 FY GUIDANCE ORLADEYO revenue $515-535 Total product revenue $540-560 Operating expenses $485-495 Operating expenses (excluding stock-based compensation) $425-435 A – From Pharmakon Advisors, $300M drawn at issuance in Q2 2023. The $324M balance above represents $300M initial issuance plus PIK interest to-date (did not elect the PIK option for Q3 2024; the PIK option has now expired)
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Traditional debt and royalty breakdown 22 Traditional Debt Commercial Royalty Initial amount $300M term loan $425M royalty upfronts Partner(s) Pharmakon (2023) RP (2020, 2021) A OMERS (2021) A Description • Rate: 3 mo. SOFR +7.00% (With PIK option: +7.25%) • Maturity: April 2028 bullet • Financial covenants: None • PIK option: 50% of interest for first six quarters • Non-recourse (payments funded with revenues) • Considered a “debt instrument” per GAAP • An effective interest rate is calculated based on forecasted royalties, which determines interest expense • Current balance = prior balance + interest expense – royalty paid • If interest expense > royalties paid, balance increases • If royalties paid > interest expense, balance decreases A – Royalty terms described on next slide September 30, 2024 December 31, 2023 Royalty financing obligations - current 33,000 23,565 Royalty financing obligations - long-term 481,775 508,034 Total royalty financing obligations 514,775 531,599 Secured term loan 314,333 303,231
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Royalty obligations: terms 23 Upfront Product Rate Tiers (Key TerritoriesB) Rate Tiers (Other MarketsB) Cumulative Payback Cap RP 2020 $125M ORLADEYO $0-350M: $350M-550M: Over $550M: 8.75% 2.75% None $0-150M: $150M-230M: Over $230M: 20% 10% None None RP 2021 $150MA ORLADEYO $0-350M: $350M-550M: Over $550M: 0.75% 1.75% None $0-150M: $150M-230M: Over $230M: 3% 2% None None OMERS 2021 $150M ORLADEYO $0-350M: $350M-550M: Over $550M: 10% 3% None $0-150M: $150M-230M: Over $230M: 20% 10% None 1.55x A – Royalty Pharma made an additional $50M equity investment in conjunction with the 2021 Royalty Purchase Agreement B – The “Key Territories” include the United States, key European markets and other markets where ORLADEYO is sold directly or through distributors. The “Other Markets” include revenue from licensees outside the Key Territories.